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The Journal of Neuroscience, December 15, 2000, 20(24):8987-8995

D₂ Dopamine Receptors in Striatal Medium Spiny Neurons Reduce L-Type Ca²⁺ Currents and Excitability via a Novel PLC1-IP₃-Calcineurin-Signaling Cascade

Salvador Hernández-López¹, Tatiana Tkatch¹, Enrique Perez-Garci², Elvira Galarraga², José Bargas², Heidi Hamm³, and D. James Surmeier^{1, 3}

¹ Department of Physiology and ³ Institute for Neuroscience, Northwestern University Medical School, Chicago, Illinois 60611, and ² Instituto de Fisiologia Celular, UNAM Apartado Postal 70-253, Mexico DF 4510

In spite of the recognition that striatal D₂ receptors are critical determinants in a variety of psychomotor disorders, the cellular mechanisms by which these receptors shape neuronal activity have remained a mystery. The studies presented here reveal that D₂ receptor stimulation in enkephalin-expressing medium spiny neurons suppresses transmembrane Ca²⁺ currents through L-type Ca²⁺ channels, resulting in diminished excitability. This modulation is mediated by G activation of phospholipase C, mobilization of intracellular Ca²⁺ stores, and activation of the calcium-dependent phosphatase calcineurin. In addition to providing a unifying mechanism to explain the apparently divergent effects of D₂ receptors in striatal medium spiny neurons, this novel signaling linkage provides a foundation for understanding how this pivotal receptor shapes striatal excitability and gene expression.

Key words: neostriatum; patch clamp; dopamine; neuromodulation; medium spiny neuron; basal ganglia; electrophysiology; single-cell RT-PCR; ion channel; calcium

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20248987-09$05.00/0

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